Artigo De: orcid, cienciavitae
Screening of Scaffolds for the Design of G-Quadruplex Ligands
Applied Sciences
— 2022 — MDPI
Informações chave
Autores:
Publicado em
18/02/2022
Resumo
In the last decade, progress has been made in G-quadruplex (G4) ligands development, but for most compounds, the ligand binding mode is speculative or based on low resolution methods, with its discovery based on structure-based approaches. Herein, we report the synthesis of small (MW < 400 Da) heterocycle compounds, containing different aromatic scaffolds, such as phenyl, quinoline, naphthalene, phenanthroline and acridine moieties, in order to explore their stabilization effect towards different DNA G4s, such as those found in c-MYC, KRAS21 and VEGF promoters, 21G human telomeric motif and pre-MIR150. The fluorescence resonance energy transfer (FRET) melting assay indicates that the acridine moiety is the most active scaffold, followed by phenanthroline. The different scaffolds are promising in terms of drug-like properties and, in general, the IC50 values of the respective heterocycle compounds are lower in a cancer cell line, when compared with a normal cell line. The acridine derivative C5NH2 has the most favorable cytotoxic profile in terms of cell selectivity.
Detalhes da publicação
Autores da comunidade :
António Manuel Rocha Paulo
ist126677
Versão da publicação
AO - Versão original do autor
Editora
MDPI
Ligação para a versão da editora
https://www.mdpi.com/journal/applsci
Título do contentor da publicação
Applied Sciences
Primeira página ou número de artigo
2170
Volume
12
Fascículo
4
ISSN
2076-3417
WoS (Web of Science)
Domínio Científico (FOS)
health-sciences - Ciências de Saúde
Palavras-chave
- G-quadruplex
- heterocycle compounds
- scaffolds
- drug-design
Idioma da publicação (código ISO)
eng - Inglês
Identificador alternativo (URI)
http://dx.doi.org/10.3390/app12042170
Acesso à publicação:
Acesso Aberto
Licença Creative Commons
CC-BY - CC-BY